Phenolic morpholines



Patented May 5, 1936 I UNITED STATES PATENT OFFICE PHENOLIC MORPHOIJNESHerman A. Bruson, Elkins Park, Pa., assignor to Riihm 8r Haas Company,Philadelphia, Pa.

No Drawing. Application February 26, 1935, p

' Serial No. 8,301

8 Claims. (01. 260-28) This invention relates to new phenolscontainpalmitic, linoleic) are soluble in fatty or in mining amorpholine group, said phenols having the eral oils, or in hydrocarbons.

probable general formula 1 These new phenolic morpholine derivatives areuseful therapeutically and as ingredients or soaps,

wetting and emulsifying agents. They may also 5 R cn,- o be used inbactericidal and insecticidal compoc sitions. I

In order to illustrate this invention, the 101- wherein R. is a phenolicaromatic nucleus. lowing examples a e given, but they e t These newcompounds may be obtained intended as limitations with respect to thephenols cording to the present invention by condensing used, time. e p ea d ot er conditions 01 any phenol having a free reactive nuclear hydrocondensation since the invention may otherwise gen atom available forcondensation with at least be practised Within the Scope of the pp onemolecular equivalent each of morpholine and I cla11115- formaldehyde. mp1 Any nuclearly hydroxylated aromatic com- 011 pound having phenolicproperties and a readily OIL-CH replaceable nuclear hydrogen atom can beused. 0

Such bodies are referred to herein broadly as CHPCHI/ phenols. Theycan'be monohydric or polyhydric phenols, and may contain also othernuclear substituents such as aliphatic, aromatic, or alicyclicNlnety-iollr grams p ol mo was mixed hydrocarbon groups, halogen,alkoxy, mm), with a solution of 87 grams morpholine (1 mol) amino, acyl,acylami110,a1ky10l,nitrile,thiocyano in 87 cc. of water. To the clearsolution obor other non-interfering radicals. Acidic groups tained,there was added dropwise While Stirring such as SOIBH interfere with thecondensation and and cooling to C.,' 100 grams of aqueous must first beneutra]jzed The term pheno1s" 30% formaldehyde solution (1 mol HCHO).The as used broadly herein includes also hydroxylated miifturewasStuffed for about'thl'ee hours {luring polynuclear aromatic cpmpoundssuch as the Whlch time an 011 separated. After standing at naphthols,hydroxy-anthracenes, hydroxy-quinomom temperature 24 hours the Oil 30lines, hydroxy caybazgles and other nuclearly was separated from thesupernatant aqueous layer hydroxylated aromatics, and washed severaltimes with hot water. In a Typical common phenols which can be used fewhours it solidified to a crystalline, waxy mass. in this condensationinclude phenol it lf on Upon recrystallization from methanol, theprodand p cresol 1 3 5 y1en 1 resorcinol or 1101; formed COIOllBSSneedles at C. ebetamaphthol, on or p phenylphen'ol It is soluble inalcohol, ether, benzene or di zylphenol, cyclohexyl-phenol,benzoylphenol, n lute caustic soda solution. Its hydrochloride,sultrophenol, chlorophenol, 2- or 4-chlOI0-0pheny1- fate, phosphate, andlactate are soluble in water. phenol, t,ef;ran1ethy1 buty1-pheno1 Ya/Y?In the above example, the phenol may be retetramethyl-butyl-resorcinol,thymol, carvacrol, placed y a molecule-fly equivalent q y of 40 terti,ry b tylor amylphenol, bis-(p-hydroxyany of its nuclear derivatives,such as 0-, m-, or phenyl) -dimethylmethane, saligenin, guaiacol, l p e-p iOdODheDOI. e Ol. catechol, hydroquinone, B-hydroxyquinoline, phigherelkylated p ol Such as thymol. caracetylamino phenol and pyrogallo1,vacrol, butyl-, amyl or octylphenols, (branched The condensation can becarried out in an Straight Chain), Xylem-l1, pitl'ophenol, y 4 inertsolvent such as water, alcohol, or dioxane. am p b n lp or u ia l t yi dThe formaldehyde used can be gaseous, aqueous, he r sp nd nghydroxy-aralkyl morpholines. or para-formaldehyde. I

The new hydroxy-aralkyl-morpholines ob- Example 2 tained are generallycrystalline when pure. Some QEQOH of them are oily, somewhat stickysirups when ca B, crude. They are soluble in both caustic alkalies CHPNand in acids such as phosphoric, lactic and acetic with which they formwater-soluble salts. Their CHPCH' I salts with the higher fatty acids,(oleic, stearic, To a mixture of 17 grams p-phenylphenol (0.1

Erample 3 CHa-CH:

. cHrcm To a mixture of 14.4 grams beta-naphthol, 35 cc. methanol, 9 cc.water and 8.7 grams morpholine, there was added while cooling, 10 gramsaqueous 30% formaldehyde solution. In about five minutes, the mixturesolidified. It was heated on the steam bath for 15 minutes under refluxto complete the reaction. When cool, the colorless crystalline productwas filtered off. After recrystallization from ethyl alcohol, it formedcolorless flakes melting at about -116 C. It is soluble in diluteaqueous caustic soda solution or in aqueous 10% phosphoric acidsolution. The yield was almost quantitative.

Example 4 I CHPCHK CHrN o Example 5 CHr-CH1\ CHi-N O CHz-CH! Cl To asolution of 20.4 grams 4-chloro-o-phenylphe- 1101 in 25 cc. of methanol,there was added 8.7 grams morpholine in 9 cc. water. While cooling andstirring, 10 grams aqueous 30% formaldehyde solution was added. Themixture was then boiled on a steam bath under reflux for 15 minutes andallowed to stand 48 hours at 25 C. The heavy sticky oil which formed wasseparated and diluted with 10 cc. methanol to aid crystallization. In afew days it solidified to a hard, colorless, crystalline mass. Afterrepeated recrystallization from methanol, the product formed colorlessplateless melting at -126 C.

Example 6.-To a solution of 11 grams resorcin- 01 (0.1 mol) in 30 cc.methanol and 8.7 grams morpholine (0.1 mol) 10 grams aqueous 30%formaldehyde was added while cooling to 20-25 C. The clear solutionobtained after standing The mixture was boiled in a stoppered flask forten days at 25 C., began to precipitate fine needles of the reactionproduct. When recrystallized from ethyl alcohol. it formed colorlessneedles melting at 207 C.

Example 7 CHr-CHQ\ on. em Cm-1K cmcn.- on when 10 Ha H:

To a solution of 22.2 grams of ,'y*tetramethyl-butylresorcinol, 35 cc.methanol, and 8.7 15 grams morpholine, there was added while cooling andstirring, 10 grams aqueous 30% formaldehyde solution. The clear solutionobtained was allowed to stand in a stoppered flask for several days at25 C. during which time two layers formed. The lower oil layer graduallycrystallized. The supernatant liquid layer was removed and 6 cc.methanol added to assist crystallization. After several hours the solidcrystalline mass was filtered off and purified by recrystallization frommethanol. The product formed colorless crystals melting at -l46 C.

The product made in the same way from a ,7-tetramethylbutylphenol was acolorless oil, which could not be crystallized, but which is readilysoluble in aqueous 10% phosphoric acid to give a foamy, soapy solution.

In the above examples, one mol each of the three components have beencondensed together. If the phenols used contain two or more freepositions ortho to the phenolic hydroxyl groups, it is possible tointroduce two or more CHa-CH:

CH:-N/

CHPCHI groups into the aromatic nucleus by employing two or more molseach of formaldehyde and morpholine per mol of the phenol.

In the examples given, the phenols used can be replaced mol for mol byany other phenolic body having a replaceable nuclear hydrogen atom. Theproducts derived from phenols or resorcinols having a long chain alkylsubstituent such as n-hexylresorcinol, amylphenol, amyl-mcresol,a,a,'y,'y-tetramethyl-butylresorcinal, and the like, by condensationwith formaldehyde and morpholine give water-soluble salts having highphenol coefllcients and possessing local anesthetic properties. Theirlactates and phosphates, particularly are extremely soluble in water togive CHI-CH! a-cm-N o CHPCHI/ wherein R represents a phenolic aromaticnucleus.

4. A condensation product of phenol, formaldehyde, and morpholine; saidcondensation product when pure, being a colorless crystalline bodymelting at about 95-96 C.

5. A condensation product of para-phenylphenol, formaldehyde andmorpholine,said condensation product when pure, being a colorless,crystalline body melting at about Bil-89 C. i

6. A condensation product of beta-naphthol, formaldehyde and morpholine,said condensation product when pure, being a colorless, crystalline bodymelting at about l15-116 C.

'7. A process for preparing a compound having the formula OHS-CHI R-CHr-0 cm-cm wherein R is a phenolic aromatic nucleus which comprisescondensing a phenol having a reactive CHrCHa into the aromatic nucleusof aphenol having atleast one reactive, replaceable hydrogen atom.

which comprises reacting on said phenol with one molecular equivalenteach oi formaldehyde morpholine for each such group to be introduced.

HERMAN A. BRUSON.

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